Inhibition of human sperm motility by contraceptive anti-eppin antibodies from infertile male monkeys: effect on cyclic adenosine monophosphate.
Epididymal protease inhibitor (eppin [official symbol, SPINLW1]) is of interest as a male contraceptive target because of its specificity and location on the human sperm surface. We have examined the effect of anti-eppin antibodies from infertile male monkeys and the effect of recombinant human semenogelin on human sperm motility. Anti-eppin antibodies significantly decreased the progressive motility of human spermatozoa as measured by decreased total distance traveled, decreased straight-line distance, and decreased velocity. Anti-eppin treatment of spermatozoa significantly increased the amount of cAMP present in nonprogressive spermatozoa; however, approximately 25% of antibody-treated spermatozoa could be rescued by the addition of cAMP-acetoxymethyl ester, indicating that anti-eppin-treated spermatozoa have a compromised ability to utilize cAMP. Addition of recombinant human semenogelin has a concentration-dependent inhibitory effect on progressive motility (increased tortuosity and decreased velocity). We tested the hypothesis that anti-eppin antibodies bound to eppin would subsequently block semenogelin binding to eppin. Anti-eppin antibodies from infertile monkeys inhibited eppin from binding to semenogelin. Addition of affinity-purified antibodies made to the dominant C-terminal epitope of eppin had an inhibitory effect on progressive motility (increased tortuosity, decreased velocity, and straight distance). Our results suggest that the eppin-semenogelin binding site is critical for the removal of semenogelin in vivo during semen liquefaction and for the initiation of progressive motility. We conclude that the eppin-semenogelin binding site on the surface of human spermatozoa is an ideal target for a nonsteroidal male contraceptive.
O'Rand
Michael G
MG
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. morand@unc.edu
Widgren
Esther E
EE
Beyler
Stan
S
Richardson
Richard T
RT
D000818:Animals; D000906:Antibodies / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D000882:Haplorhini / Q000276:immunology; D006801:Humans; D007248:Infertility, Male / Q000276:immunology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D053491:Proteinase Inhibitory Proteins, Secretory / Q000276:immunology* / Q000378:metabolism; D029607:Seminal Vesicle Secretory Proteins / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects* / Q000276:immunology
D000906:Antibodies; D003272:Contraceptive Agents, Male; C431553:Eppin protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen; D000242:Cyclic AMP